Mouse anti-human monoclonal antibodies specific for tumor-associated antigens of gastrointestinal adenocarcinomas, melanoma and lung carcinomas will be used for human immunotherapy. In preclinical studies, these monoclonal anti-tumor antibodies of Gamma-2a isotype are tumoricidal in vitro and inhibit tumor growth in vivo. The same antibodies bind preferentially to tumor cells in ex vivo perfused human colons containing cancer. A limited phase I clinical trial for one of the anti-colon carcinoma monoclonal antibodies has been completed. This proposal would expand the scope of the immunotherapeutic trial using this anti-colon carcinoma antibody and other tumoricidal monocilonal antibodies against gastrointestinal cancers, melanoma and eventually lung adenocarcinoma. Antibody, or autologous leukocytes preincubated with antibody, will be infused intravenously into the hepatic artery of patients with metastatic disease. The direct effect on the tumor will be measured by serial CAT scans. Tumor samples obtained before and after antibody administration will be assayed for immune cell infiltration, monoclonal antibody-defined antigen expression and modulation, and for the presence of bound specific mouse immunoglobulin (monoclonal antibody). Duration of the antibody presence in patient serum and kinetics of development of human anti-mouse immunoglobulin will be studied. Cytotoxic conjugates of monoclonal anti-tumor antibodies with natural toxins or chemotherapeutic agents will be tested in animal systems and incorporated into a phase I clinical trial. Strategies to allow re-treatment with mouse monoclonal antibody will be explored. Treatment effect on the tumor will be monitored by computed tomography, immunopathologic and serologic studies, and patient survival.